Medical and health-care fields, research and development sectors typically use autoclaves or steam sterilizers to sterilize microbially-contaminated medical instruments or test devices for their reuse. The autoclave is used for a sterilization technology that comprises for example, putting dirty medical instruments in a compression chamber, keeping for several tens of minutes the instruments within the chamber of a pressurized, heated and humid atmosphere, and hydrolyzing and decomposing microorganism biopolymer into their extinction at a high temperature to annihilate all bacteria and viruses. One such sterilizing process with autoclave, however, is defective because it disadvantageously requires heating an inside of autoclave vessel up to a temperature of 130 degrees C. that is not applicable to sterilization of low heat-resistant instruments for example made of rubber. This process also raises a further problem with sterilization of plastic instruments because they are subject to heating cycles that cause plastic instruments to repetitively, physically and thermally expand and contract. This allows pressurized water vapor to penetrate into interstices inherently formed on plastics under pressure of approximately 2 atmospheres while facilitating deterioration of plastics.
An alternative sterilizing technology with gas of ethylene oxide (C2H4O) (EOG) can be applied to disinfection of lower heat- and moisture-resistant rubbers and plastics because the technology can work at a lower temperature, at a lower pressure and at a lower humidity than those in autoclave. However, it must utilize highly reactive ethylene oxide gas that disadvantageously brings dangers for people because of its ignitability and explodability under pressure. Also, it is very troublesome to handle and has high toxicity to human body. Human inhalation of ethylene oxide gas may cause a variety of symptoms for example membrane irritation of upper airway, vomiting and headache, and it may be a carcinogen damaging zoetic deoxyribonucleic acid. The United States Pharmacopeia (USP) has strengthened the regulation for usage of ethylene oxide gas that thereby increases needs of better alternative.
Now, one of high-profile sterilants is nitrogen oxide that is relatively easy to handle for sterilization with neither application of heat and pressure to the sterilant. Nitrogen oxide is a generic or collective name of nitrogen-oxygen compound groups consisting of nitric monoxide (NO), nitrogen dioxide (NO2), nitrous oxide (dinitrogen oxide) (N2O), dinitrogen trioxide (N2O3), dinitrogen tetraoxide (N2O4) and dinitrogen pentoxide (N2O5). Patent Document 1 below listed discloses a system for sterilizing and decontamianting a contaminated object, i.e. a dirty medical device by exposing it to one or more nitrogen oxide sterilizing gases selected from groups of NO, NO2, NO3, N2O3, N2O4, N2O5, N2O and their mixture. The system stores sterilant feedstock that is turned into nitrogen oxide gas to thereby sterilize the object within a hermetically sealed chamber.
Patent Document 2 mentioned below discloses a sterilization apparatus that comprises: a sterile chamber to define a hermetically closed space, contaminated objects arranged within the sterile chamber, the objects including medical instruments such as scalpel, forceps, catheter and food packaging materials such as packaging sheets, trays, bottles and a plasma generator for producing nitrogen oxide gas at an atmospheric pressure to introduce the gas from plasma generator through catalysts into the sterile chamber and to expose the dirty objects to nitrogen oxide gas for their sterilization. The plasma generator comprises a microwave generator and a plasma activation nozzle for receiving microwave energy from the microwave generator to convert feedstock gas into plasma. Thus, Patent Document 2 shows production of nitrogen oxide plasma derived from nitrogen and oxygen in feedstock gas.
Patent document 1 shows usage of a reaction chamber to generate nitrogen oxide gas by reaction of oxalic acid and diazeniumdiolate compound [R3—C(R1)x(N2O2R2)y] as a feedstock coming into sterilant gas or by reaction of acid and another type of sterilant-gas occurring feedstock. However, these reactions are disadvantageous because they require proper and strict controls of the reaction conditions in reaction chamber when mixing a plurality of materials within reaction chamber to turn them into nitrogen oxide gas to be sent to a sterilization chamber, and failure of proper controls for the reactive conditions would lead to unstable concentration in generated nitrogen oxide that would result in insufficient disinfection of an object in sterilization chamber. In another aspect, with excessive amount of nitrogen oxide fed into sterilization chamber, that would cause unfavorable adherence of nitrogen oxide on sterilized medical instruments at a high concentration against their subsequent safe usage. Also, in fact, actual medical practices would find difficulty in applying sterilization to medical instruments if each sterilization requires mixing of solid feedstock and acid. In addition, acids are dangerous when handling for transportation and storage.
Patent Document 2 discloses a sterilization apparatus for generating nitrogen oxide gas through plasma gasification that utilizes nitrogen and oxygen in the air as raw materials, however, it has a very low efficiency in generation of nitrogen oxide gas although not involving any risk in conveying and storing the raw materials. For that reason, the sterilization apparatus of Patent Document 2 is defective because it must spend so much time and high energy cost not only in preparation for generating and filling nitrogen oxide gas inside of sterilization chamber prior to the start of sterilization but also in completed sterilization of the object while keeping a predetermined concentration of nitrogen oxide within sterilization chamber. In addition, the apparatus in Patent Document 2 must generate nitrogen oxide in a plasma gasifier and further undesirably convert it into highly sterilizing nitrogen dioxide by means of expensive catalyst such as platinum or palladium that may raise the production cost.
Moreover, previous studies and researches including Patent Documents 1 and 2 have never proposed any recovery method for efficiently and completely collecting a sterilant from a sterilization chamber after sterilization. Therefore, prior art sterilizations are dangerous because they cannot completely remove poisonous sterilant at a specific density range particularly around specific configurations of medical instruments to be safely reused or recycled after sterilization.
Sterilization chambers such as clean rooms, clean booths or isolators are kept in an almost aseptic condition, preventing intrusion of bacteria, microorganism and dust into the chamber for pharmaceutical research, manufacture and inspection. Concentration of airborne particles is controlled within clean rooms with their inner volume of approximately 20 to 300 m3 wherein inflow, generation and stagnation of microparticles are controlled to their minimum while also controlling temperature, humidity and pressure of clean rooms as necessary. Clean booths have been developed to clean and sterilize a small working space to define a simplified clean room of its inner volume approximately 2 to 30 m3. Isolators form a large chamber of its inner volume of approximately 2 to 20 m3 isolated from the atmosphere to conduct inner operations within the chamber through external manual manipulations with rubber gloves provided before a transparent front wall of each isolator.
Air within each clean room is vacuumed up or circulated by an air blower to remove airborne microparticles through filters and thereby keep clean rooms in the almost sterile condition. In this way, removal of airborne microparticles basically allows for exclusion of microorganisms and bacteria to thereby prevent microbial contamination in clean room. However, in fact, such filtering microparticles alone fails to fully eliminate bacteria because it cannot completely remove bacteria in the stagnant air around corners of clean rooms. Taking in air and blowing air through filters cannot fully remove contaminants such as microorganisms adhering or attaching onto wall and floor surfaces in clean room. Thus, such air filtering methods require periodical sterilization of inside in clean rooms.
A gas sterilization is known for disinfecting treatment of unsterilized objects such as inside of clean rooms utilizing a formaldehyde, hydrogen peroxide (H2O2) or ozone (O3) gas sterilizer. One such gas sterilizer is used to first feed a sterilizing gas from a gas generator or gas tank into a sterilization chamber to repletion, and then to keep the chamber in the gas repletion condition for a certain period of time to annihilate microorganisms and bacteria floating in the air or adhering on sterilization chamber walls.
The gas sterilization can also be applied to sterilization of microbially contaminated medical devices for their recycle. Sterilization of medical instruments typically utilizes autoclaves (or high-pressure steam sterilizers), however, they are defective because they disadvantageously require heating inside of an autoclave vessel up to a temperature of 130 degrees C., and so autoclaves cannot be applied to low heat-resistant instruments for example made of rubber because they must use pressurized water vapor that penetrates into interstices inherently formed on plastics under the pressure of approximately 2 atmospheres while facilitating deterioration of plastics. Accordingly, rather gas sterilization is advantageous to disinfection of heat- and pressure-irresistible medical instruments.
Gas sterilization of medical instruments often uses ethylene oxide gas (EOG). Ethylene oxide is a transparent, colorless and ether-smelling substance of the evaporation temperature at approximately 20 degrees C. Ethylene oxide gas for sterilization is diluted with carbon dioxide gas to prepare a mixed gas filled in a high-pressure vessel that consists of approximately 20% ethylene oxide and approximately 80% carbon dioxide gas. The mixed gas with ethylene oxide is supplied from high-pressure vessel into a clean room or into a spatial area of a sterilization chamber kept at a predetermined ethylene oxide gas concentration where medical instruments are disposed for a certain period of time for their sterilization.
Patent Document 3 discloses a sterilization system for disinfecting an isolator with hydrogen peroxide for asepsis of a spatial area. The system comprises a sterilizing gas source, an isolator and gas conduits for connecting the gas source and isolator, wherein the gas source has an evaporator to vaporize hydrogen peroxide, an ejector for dropping hydrogen peroxide liquid in the evaporator, and a heater for heating air sent to the evaporator to sterilize inside of the isolator with hydrogen peroxide gas.
Patent Document 2 below discloses an apparatus for antisepticizing unsterilized objects (such as medical instruments or containers in use for medical purpose) by an ozone sterilizer in a sterile area. In this case, the objects in sterile area are exposed to ozone gas for a certain period of time, and then, air is introduced into sterile area through an aeration line connected thereto to discharge ozone gas.
Ethylene oxide gas has the high toxicity to human body that may cause irritation on upper airway membranes, vomiting and headache, and that may be a carcinogen damaging deoxyribonucleic acid (DNA). Thus, it would be too dangerous for human health to inhale remaining ethylene oxide gas after sterilization.
Patent Document 3 shows an isolator system that requires a lot of energy for a heater to heat and vaporize hydrogen peroxide of the boiling point 141 degrees C., and the isolator is further defective because hydrogen peroxide steam of a very high temperature may denature and deteriorate heat-labile materials (rubber or resin) in the isolator. Also, the isolator system in Patent Document 3 fails to precisely control a supply amount of hydrogen peroxide, and the excessive supply amount may lead to a corrosion to metallic components in isolator and a residue of hydrogen peroxide after sterilization, and the insufficient supply amount may fail to completely destroy microorganisms and bacteria in isolator. In general, hydrogen peroxide is highly reactive and intensely degradable at a room temperature and may ignite and explode with self-decomposition particularly at a high concentration. Attachment of hydrogen peroxide to a human skin will develop painful vitiligo on the skin, and therefore, it is very troublesome to handle the substance for transportation and storage. Hydrogen peroxide is also highly corrosive to metallic materials.
Patent Document 4 teaches an ozone sterilizer that controls interior pressure in a sterile area to a negative level below normal pressure to then supply ozone into the sterile area. This ozone sterilizer is disadvantageous because it generates ozone from air source with its too low efficiency and takes a long time to replete ozone of a predetermined concentration in the sterile area of large volume, and it fails to precisely control the generated amount of ozone for exact adjustment of ozone concentration in the sterile area. The ozone sterilizer requires an ozone generator that generates ozone at the site of sterilization immediately before its usage because ozone is so chemically-unstable as to inherently and gradually proceed with the decomposition at a room temperature. For that reason, the ozone sterilizer must be made into a larger size of the whole sterilizing system that increases equipment installation and running costs inclusive of operating electricity costs. Also, ozone is too dangerous because of its strong oxidizability to deadly poison at high concentration, and human inhalation of ozone causes his or her viscera to be oxidized to erosion.
When nitrogen oxide is used as a sterilant in Patent Document 1, it must mix different kinds of materials within a reaction chamber to generate and supply a nitrogen oxide gas into spatial area while it is impossible to detect and control a precise yield of nitrogen oxide gas and also to be unable to feed nitrogen oxide gas at a predetermined precise concentration into the spatial area against full sterilization of medical devices therein. Adversely, excessive amount of nitrogen oxide into the chamber, would cause nitrogen oxide at the elevated concentration to unfavorably remain around and adhere on the sterilized objects to commit a safety violation. Also, if every sterilization requires the mixing procedure of solid sterile feedstock and acid, in fact it would be very difficult to be adopted in medical practice for sterilization of clean rooms and medical instruments. In addition, acids involve much danger in its usage and handling for transportation and storage.
[Patent Document 1] Japanese Patent Disclosure No. 2009-542333
[Patent Document 2] Japanese Patent Disclosure No. 2011-4802
[Patent Document 3] Japanese Patent Disclosure No. 2006-68122
[Patent Document 4] Japanese Patent Disclosure No. 2001-340432